Tissue culture systems have been developed in which neuromuscular junctions form rapidly de novo. Using high resolution Nomarski optics and electrophysiologic techniques the development and distribution of acetylcholine receptors on the muscle surface membrane have been continuously monitored on single cells during early stages of synapse formation. A small computer has been used to detect the first signs of neuromuscular transmission. A technique to freeze fracture monolayer cultures has been developed in an attempt to determine the intramembranous ultrastructural correlates of receptor distribution and developing neuromuscular junctions.